Huntington's Disease (HD) is an inherited disease that results from expansion of a trinucleotide (CAG, cytosine/adenine/guanine) repeat that encodes a polyglutamine tract in the huntingtin protein. Psychiatric symptoms, including irritability and aggression, are common in HD patients. These are among the most distressing aspects of the disease. They have adverse effects on daily life and often result in institutionalization. Despite the frequent occurrence and severe consequences of irritability and aggression in HD, these symptoms have received little attention to date. Effective treatments are lacking and well-validated scales for measuring changes in these symptoms are not available. Faced with a significant unmet need, neurologists cannot currently determine whether new drug therapies might be useful in treating neuropsychiatric symptoms in HD. The Phase II clinical trial we propose in HD patients (n=108), A randomized, placebo controlled, double blind, multi-center study to assess the tolerability of SRX246 in irritable/aggressive subjects wit Huntington's Disease (HD), will allow us to rigorously evaluate the tolerability of a potential ne drug for the treatment of irritability and aggression. It will also provide additional safety data n the compound and explore various rating scales for the assessment of changes in these symptoms. Thus, we will obtain critical data that can be used to plan future Phase II or III clinicl trials of drugs that might blunt irritability and aggression in HD. The compound that we propose to test is SRX246, a first-in-class vasopressin 1a (V1a) receptor antagonist. SRX246 crosses the blood-brain barrier following oral administration, exhibits high affinity and selectivity for is target receptor, has a strong safety profile, is well-tolerated in healthy volunteers, and has excellent pharmacokinetics. Extensive preclinical pharmacology studies and an experimental medicine fMRI study in healthy volunteers have shown that SRX246 has CNS effects after oral administration and that it modulates brain circuits involved in responses to stimuli that elicit aggression/fear. These findings strongly suggest that SRX246 might have a beneficial effect on the irritability and aggression seen in a sizable proportion of HD patients. The proposed project will generate data needed to plan a future clinical trial that can rigorously test SRX246 for efficacy as a treatment for irritability and aggression.